The objectives of this project are to document senescent changes in the capacities of mice to develop and display delayed hypersensitivity to nonreplicating purified antigens, and to investigate the causes for these changes. Medium-lived CAF1 and CF-1, and short-lived NZB mice will be sensitized with conalbumin or methylated human serum albumin in incomplete Freund adjuvant at intervals ranging from youth through senescence and tested for specific dermal reactivity to these antigens 3, 5, and 7 weeks after sensitization. Expected decreases in delayed hypersensitivity in older mice will be analyzed in vivo and in vitro to determine which alterations in immunocyte, organ, or general physiologic responses account for decreasing responsiveness, whether the decreases are active or passive effects, whether they are restricted to either induction or elicitation in delayed hypersensitivity, how they emerge, and how they can be controlled. In vivo analyses will depend largely on cell destruction, modification and transfer experiments; typically, in vitro tests will reveal whether cells which can react specifically with antigen are present in an unreactive animal but are being suppressed therein. The above experiments will be supplemented with experiments in mice which have been altered immunologically, surgically, or with drugs or irradiation to age prematurely. Alterations would include adult thymectomy, autoimmunization with thymus extracts, and prolonged series of injections of antiserum to thymus and/or pituitary gland. Data obtained from this project are expected to help explain loss with aging in man of cell-mediated immunity and suggests ways of delaying or preventing such loss.